General Discussion

Heavy metal poisoning is the accumulation of heavy metals, in toxic amounts, in the soft tissues of the body. Symptoms and physical findings associated with heavy metal poisoning vary according to the metal accumulated. Many of the heavy metals, such as zinc, copper, chromium, iron and manganese, are essential to body function in very small amounts. But, if these metals accumulate in the body in concentrations sufficient to cause poisoning, then serious damage may occur. The heavy metals most commonly associated with poisoning of humans are lead, mercury, arsenic and cadmium. Heavy metal poisoning may occur as a result of industrial exposure, air or water pollution, foods, medicines, improperly coated food containers, or the ingestion of lead-based paints.

Signs & Symptoms

The symptoms of heavy metal poisoning vary according to which type of metal overexposure is involved. Some specific examples are:

ARSENIC POISONING

Arsenic is used in the manufacture of pesticides. The gas from arsenic also has some industrial uses. Overexposure may cause headaches, drowsiness, confusion, seizures, and life-threatening complications. Neurological symptoms include brain damage (encephalopathy), nerve disease of the extremities (peripheral neuropathy), pericapillary hemorrhages within the white matter, and loss or deficiency of the fatty coverings (myelin) around these nerve fibers (demyelination). Skin problems include transverse white bands on the fingernails (mees’ lines) and excessive accumulation of fluid in the soft layers of tissue below the skin (edema). Gastrointestinal symptoms include a flu-like illness (gastroenteritis) that is characterized by vomiting; abdominal pain; fever; and diarrhea, which, in some cases, may be bloody. Other symptoms include breakdown of the hemoglobin of red blood cells (hemolysis), a low level of iron in the red blood cells (anemia), and low blood pressure (hypotension). Some individuals may experience a garlic-like odor that may be detectable on the breath.

In cases of chronic poisoning, weakness, muscle aches, chills, and fever may develop. The onset of symptoms in chronic arsenic poisoning is about two to eight weeks after exposure. Skin and nail symptoms include hardened patches of skin (hyperkeratosis) with unusually deep creases on the palms of the hands and the soles of the feet, unusual darkening of certain areas of the skin (hyperpigmentation), transverse white bands on the fingernails (mees’ lines), and a scale like inflammation of the skin (exfoliative dermatitis). Other symptoms include inflammation of sensory and motor nerves (polyneuritis) and the mucose membrane lining the throat.

Inorganic arsenic accumulates in the liver, spleen, kidneys, lungs, and gastrointestinal tract. It then passes through these sites but leaves a residue in tissues such as skin, hair, and nails. Symptoms of acute inorganic arsenic poisoning include severe burning of the mouth and throat, abdominal pain, nausea, vomiting, diarrhea, low blood pressure (hypotension), and muscle spasms. Individuals with severe inorganic arsenic poisoning may experience heart problems (cardiomyopathy); accumulation of acid in the tubes of the kidneys (renal tubular acidosis); breakdown of the hemoglobin of red blood cells (hemolysis); irregular heart rhythms (ventricular arrhythmias); coma; seizures; bleeding within the intestines (intestinal hemorrhage); and yellowing of the skin, mucous membranes, and whites of the eyes (jaundice).

CADMIUM POISONING

Cadmium is used for many items, including electroplating, storage batteries, vapor lamps and in some solders. The onset of symptoms may be delayed for two to four hours after exposure. Overexposure may cause fatigue, headaches, nausea, vomiting, abdominal cramps, diarrhea, and fever. In addition, progressive loss of lung function (emphysema), abnormal buildup of fluid within the lungs (pulmonary edema), and breathlessness (dyspnea) may also be present. In some cases, affected individuals may exhibit increased salivation; yellowing of the teeth; an unusually rapid heart beat (tachycardia); low levels of iron within the red blood cells (anemia); bluish discoloration (cyanosis) of the skin and mucous membranes due to insufficient oxygen supply to these tissues; and/or an impaired sense of smell (anosmia). Individuals with cadmium poisoning may also experience improper functioning of the canals with the kidney (renal tubular dysfunction) characterized by excretion of abnormally high levels of protein in the urine (proteinuria), minor changes in liver function, and/or softening of certain bones (osteomalacia).

CHROMIUM POISONING

Chromium is used in the manufacture of cars, glass, pottery and linoleum. Exposure to too much chromium may cause lung and respiratory tract cancer as well as kidney diseases. In addition, overexposure to chromium may also cause gastrointestinal symptoms, such as diarrhea and vomiting, often with blood. Symptoms may lead to severe water-electrolyte disorders, increased mild acidity of blood and body tissues (acidosis), and/or inadequate blood flow to its tissues resulting in shock. Lesions on the kidneys, liver, and muscular layer of the heart (myocardium) may also develop.

Lead production workers, battery plant workers, welders and solders may be overexposed to lead if proper precautions are not taken. Lead is stored in the bone but may affect any organ system. The effects of lead poisoning varies depending on the age of the individual and the amount of exposure.

In children, symptoms vary depending upon the degree of exposure to lead. Some affected individuals may not have any noticeable symptoms. Symptoms usually develop over a three to six week time period. Lead overexposure may cause children to be less playful, clumsier, irritable, and sluggish (lethargic). In some cases, symptoms include headaches, vomiting, abdominal pain, lack of appetite (anorexia), constipation, slurred speech (dysarthria), changes in kidney function, unusually high amounts of protein in the blood (hyperproteinemia), and unusually pale skin (pallor) resulting from a low level of iron in the red blood cells (anemia). Neurological symptoms associated with lead overexposure include an impaired ability to coordinate voluntary movements (ataxia), brain damage (encephalopathy), seizures, convulsions, swelling of the optic nerve (papilledema), and/or impaired consciousness. Some affected children experience learning or behavioral problems such as mental retardation and selective deficits in language, cognitive function, balance, behavior, and school performance. In some cases, symptoms may be life-threatening.

Lead is excreted in urine and feces. However, it may also appear in hair, nails, sweat, saliva, and breast milk.

MANGANESE POISONING

Manganese is used as a purifying agent in the production of several metals. Symptoms associated with overexposure to manganese may include damage to the central nervous system and pneumonia. Additional symptoms and physical findings include weakness, fatigue, confusion, hallucinations, odd or awkward manner of walking (gait), muscle spasms (dystonia), rigidity of the trunk, stiffness, awkwardness of the limbs, tremors of the hands, and psychiatric abnormalities.

MERCURY POISONING

Mercury is used by dental assistants and hygienists, and chemical workers. Mercury can affect the lungs, kidneys, brain, and/or skin. Symptoms of mercury poisoning include fatigue, depression, sluggishness (letheragy), irritability, and headaches.

There may be behavioral and neurological changes associated with overexposure to mercury poisoning, such as excitability and quick-tempered behavior, lack of concentration, and loss of memory. Shock and permanent brain damage may also be result from mercury poisoning. Some affected individuals experience mental confusion. A progressive cerebellar syndrome with impaired ability to coordinate voluntary movements (ataxia) of the arms may also be present. Abnormal involuntary movements of the body such as uncontrolled jerky movements combined with slow, writhing movements (choreoathetosis) are common. Additional symptoms include non-inflammatory degenerative disease of the nerves (polyneuropathy); impaired ability to coordinate voluntary movements (cerebellar ataxia); tremors of the legs and arms and, in some cases, of the tongue and lips; seizures; and/or slurred speech (dysarthria). Changes in mood, behavior, and consciousness may also occur.

In some cases of chronic exposure to inorganic mercury a personality disorder known as erethism or mad hatter syndrome may occur. Symptoms associated with mad hatter syndrome include memory loss, excessive shyness, abnormal excitability, and/or insomnia. This syndrome was described in workers with occupational exposure to mercury in the felt-hat industry.

Many affected individual experience sensory impairments such as visual problems (e.g. constriction of visual fields, tunnel vision, and blindness) as well as hearing loss.

Some individuals may experience skin changes such as painful swelling and pink coloration of the fingers and toes (acrodynia); persistent redness or inflammation of the skin (erythema); extreme sensitivity (hyperesthesia) of the affected areas; and tingling and sensory disturbances.

In some cases, other affected individuals may experience stomach and intestinal disturbances; kidney damage; dehydration; acute renal failure; inflammation of the gums (gingivitis); severe local irritation of the mouth and pharynx, accompanied by vomiting; and/or abdominal cramps with bloody diarrhea.

Additional metals that may cause poisoning include antimony, aluminum, barium, bismuth, copper, gold, iron, lithium, platinum, silver, tin, and zinc. Common symptoms of poisoning from these metals may include gastrointestinal, renal, and neurological symptoms, such as headaches, irritability, psychosis, stupor, coma, and convulsions.

Antimony is used for hardening lead, and in the manufacture of batteries and cables. It may possibly cause lung disease and skin cancer, especially in those who smoke.

Copper is used in the manufacture of electrical wires. It may cause a flu-like reaction called metal fume disease and disturbances in the blood.

Lithium is used to make glasses and pharmaceuticals. Lithium may cause diseases of the stomach, intestinal tract, central nervous system, and kidneys.

Overexposure to silver may cause a gray discoloration of the skin, hair and internal organs. Additional symptoms may include nausea, vomiting, and diarrhea.

Some cases of overexposure to nickel have been associated an increased risk of lung cancer.

Overexposure to selenium may cause irritation of the respiratory system, gastrointestinal tract, and eyes; inflammation of the liver; loss of hair (alopecia); loss of skin color (depigmentation); and peripheral nerve damage.

Overexposure to tin may damage the nervous system and cause psychomotor disturbances including tremor, convulsions, hallucinations, and psychotic behavior.

Aluminum containers used in the manufacture and processing of some foods, cosmetics and medicines, and also for water purification. Overexposure to aluminum may cause brain damage (encephalopathy).

Causes

Heavy metal poisoning is a result of the toxic accumulation of certain metals. Such metals compete with and replace certain essential minerals in the course of which any of several of the body’s organ systems may be affected.

Arsenic poisoning may be caused by medications including Fowler’s solution (potassium arsenite) and some topical creams used in the treatment of some skin conditions. Ingestion of herbicides, insecticides, pesticides, fungicides, or rodenticides containing arsenic may cause arsenic poisoning. Occupational exposure to arsenic in the manufacture of paints, enamels, glass, and metals may cause arsenic poisoning. Other forms of occupational exposure include galvanizing, soldering, etching, lead plating, smelting, and wood preserving. Arsenic is also found in contaminated water, seafood, and algae.

Cadmium poisoning may be caused by ingestion of food (e.g. grains, cereals, and leafy vegetables) and cigarette smoke. Occupational exposure to cadmium in metal plating, battery, and plastics industries may also occur.

Lead poisoning may be caused by exposure (e.g. chewing or ingestion) to deteriorating lead paint in older houses. Occupational exposure to lead in painting, smelting, firearms instruction, automotive repair, brass or cooper foundries, printing, battery manufacturing, mining, brass foundry, gasoline, glass, and bridge, tunnel and elevated highway construction may also occur. Another cause of lead poisoning is through the contamination of water from lead pipes. Additional causes of lead poisoning include calcium products, progressive hair dyes, kajal, surma, kohl, and foreign digestive remedies.

Manganese poisoning may be caused by chronic inhalation and ingestion of manganese particles. Occupational exposure to manganese in mining and separating manganese ore may also occur.

Mercury poisoning may be caused by exposure to large amounts of mercury in the manufacturing of thermometers, mirrors, incandescent lights, x-ray machines, and vacuum pumps. Another cause of mercury poisoning is contaminated water and fish. Children often are exposed to mercury through paint, calomel, teething powder, and mercuric fungicide used in washing diapers. Additional causes of mercury poisoning is exposure to mercury in thermometers, dental amalgams, and some batteries.

Phosphorus poisoning may be caused by insecticides such as tetraethylpyrophosphate.

Thallium poisoning may be caused by ingestion of rodenticides containing thallium. Thallium in pesticides, insecticides, metal alloys, and fireworks can be absorbed through skin as well as through ingestion and inhalation.

Affected Populations

Heavy metal poisoning can affect males and females in equal numbers, depending on exposure. Outbreaks of this type of poisoning have occurred in the United States during the past several years from imported plates and cookware that were not properly coated to prevent heavy metals from contaminating food.

In the United States, lead poisoning most often affects children between one and three years old.

Lead poisoning affects adults less often than children. In the last 20 years, statistics show the number of children with potentially harmful blood lead levels has dropped 85 percent.

Mercury poisoning is unusual in children. There have been large outbreaks in Australia and France of bismuth poisoning.

Related Disorders

Symptoms of the following disorders can be similar to those of heavy metal poisoning. Comparisons may be useful for a differential diagnosis:

Metal fume fever includes a variety of symptoms, such as a general feeling of ill health (malaise), chills, and fever. Affected individuals may have excessive thirst and a metallic taste in their mouth. Symptoms usually subside spontaneously in six to 12 hours. A classic case would occur when galvanized steel is welded in a poorly ventilated area.

The following disorders may be associated with heavy metal poisoning as secondary characteristics. They are not necessary for a differential diagnosis.

Fanconi’s anemia is a blood disorder, which is a familial form of aplastic anemia. Children with this disorder bruise easily and experience nosebleeds. It may be caused by genetic and environmental interactions. Fanconi’s syndrome can be acquired instead of inherited due to acute lead poisoning. (For more information on this disorder, choose “Fanconi’s Anemia” as your search term in the Rare Disease Database.)

Wilson’s disease is a genetic disorder characterized by excess storage of copper in the body’s tissues, particularly in the liver, brain and corneas of the eyes. The disorder occurs without overexposure to copper and is due to a metabolic defect. (For more information on this disorder, choose “Wilson Disease” as your search term in the Rare Disease Database.)

Diagnosis

The diagnosis of arsenic poisoning can be confirmed by discovering increased levels of arsenic in the hair, nails, and urine. An x-ray of abdomen may show ingested arsenic which is not penetrable by x-rays (radiopaque).

The diagnosis of lead poisoning may be suspected based upon appreciation of the causative factors, a high index of suspicion, and certain laboratory tests for levels of lead in the blood. Other indicators of lead poisoning include an elevation of free erthrocytic protoporphyrins, inhibition of ALA-D activity, elevated lead in the hair, increased lead content of deciduous teeth, estimation of urinary coproporphytins, zinc protoporphyrin levels. A spinal tap may also be helpful in the diagnosis of lead poisoning. The LEADCARE In Office Test System has been approved by the FDA as a portable blood lead screening kit for health professionals' use to test for lead poisoning.

Standard Therapies

Treatment

The main treatment of heavy metal poisoning is termination of exposure to the metal. Treatment also consists of the use of various chelating agents that cause the toxic (poison) element to bind with the drug and be excreted in the urine. Three common drugs for treatment of metal poisoning are: BA. (Dimercaprol), Calcium EDTA (Calcium Disodium Versenate) and Penicillamine. Each of these work by binding actions that permit the metals to be eliminated from the body through the urine.

Treatment should also be symptomatic and supportive. In some cases, pumping of the stomach (gastric lavage) will remove some ingested metals. In the case of inhaled poisons, affected individuals should be removed from the contaminated environment and their respiration supported.

Occupational exposure to heavy metals requires prevention through the use of masks and protective clothing.

In cases of swelling of the brain (cerebral edema), treatment with a diuretic called Mannitol, and corticosteroid drugs, along with intracranial monitoring, is required.

Kidney failure may call for hemodialysis and/or other special treatment.

In 1991 the FDA approved the drug succimer (Chemet) for the treatment of children with severe lead poisoning. Chemet is manufactured by Johnson & Johnson Co.

There is no proven effective therapy for the treatment of cadmium poisoning.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

Two orphan drugs are being tested for the treatment of heavy metal poisoning.

In the treatment of iron poisoning, the drug Bio-Rescue (40SD02 and 25SD04) is being developed by Biomedical Frontiers, Inc. of Minneapolis, MN, in alliance with Hemosol.

Mercury poisoning is being treated by the drug, Chemet (Succimer), which is being developed by McNeil Consumer Products, Co., Ft. Washington, PA.

NORD's Rare Disease Database provides brief introductions for patients and their families to more than 1,200 rare diseases. This is not a comprehensive database since there are nearly 7,000 diseases considered rare in the U.S. We add new topics as we are able to do so, with the help of rare disease medical experts.

If you are seeking information about a rare disease that is not in this database, we would suggest contacting the Genetic and Rare Diseases Information Center (GARD) at the National Institutes of Health. NIH has the most complete database of rare diseases in the U.S.

Representatives of patient organizations whose medical advisors are interested in assisting NORD in creating a report on a disease not currently covered in this database may write to orphan@rarediseases.org.